Practice question
Question
Which of the following describes the function of PITX1 in limb development?
Explanation
PITX1 is a paired-type homeodomain transcription factor restricted to hindlimb mesenchyme, serving as master hindlimb identity regulator throughout development. It directly activates TBX4 expression and represses forelimb genes, controlling hindlimb-specific characteristics including elongated femur shape, patella formation, tendon pattern and Pitx1-dependent hindlimb muscle via Tbx4-FGF10 axis and Hox genes. Transgenic loss or Pitx1 mutant mice show partial forelimb-like transformation of hindlimbs, altered knee articulation and clubfoot phenotypes. It does not maintain FGF8 directly, inhibit forelimb growth globally, or block Wnt signaling. Its role is activating hindlimb-specific program.
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